Multi-Domain Exercise and Memory in Adults Relative to ApoE Genotype: A fMRI Study

Sponsor

National Taiwan Normal University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05068271

Collaborator

(none)

100

Enrollment

Locations

Arms

40.7

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The current project utilizes a single-blinded, double arm, 6-month randomized controlled trial to assess the effects of a multi-domain exercise program on memory performance, as well as cortical activities during the memory tasks in cognitively intact adults (i.e., 45-70 years). In addition, the potential moderator role of apolipoprotein epsilon-4 (ApoE e4) status and the mediator role of the brain-derived neurotrophic factor (BDNF) will be explored.

Condition or Disease	Intervention/Treatment	Phase
Exercise Training Executive Function Aging	Behavioral: Multi-Domain Exercise Program Behavioral: Control Group	N/A

Detailed Description

Aging has been adversely associated with the deterioration of cognitive and brain functions. Most research on the effects of regular exercise on cognitive and brain functions has been focused on exercise programs with a single mode of exercise. Studies focusing on the effects of exercise programs with multi-domains on cognitive function and cortical functionality are sparse in late-middle-aged and older adults. In addition, while growing evidence has revealed the beneficial effects of regular exercise on cognitive function, scientific evidence regarding the effects of multi-domain exercise programs on cognitive function and brain function in late-middle-aged and older adults who are with or without the genetic risk for Alzheimer's disease (AD) is scarce. Lastly, the potential mediator role of the brain-derived neurotrophic factor (BDNF) in individuals is required to be explored.

In the current study, a single-blinded, double arm, 6-month randomized controlled trial has been utilized to assess the effects of a multi-domain exercise program containing multiple physical fitness components, meditation, and social interaction on memory, as well as cortical functionalities during the memory tasks in cognitively intact adults (i.e., 45-70 years). Specifically, the project aims to examine: (1) the causal links between a multi-domain exercise program composed of various physical fitness components, meditation, and social interaction against a control group on the memory performance in cognitively intact adults aged between 45 and 70 years with or without a genetic risk for AD, (2) the cortical functionality through functional images collected through a series of functional magnetic resonance images (fMRI), and (3) the potential influence of apolipoprotein epsilon-4 (ApoE e4) and BDNF on the effects of exercise.

One hundred eligible individuals will participate in the current study and will be randomly assigned into either the 6-month multi-domain exercise group (exercise group) or the online educational course group (control group).

All participants' physical fitness, cognitive function, and cortical functionalities via fMRI scanning will be assessed at the Baseline (Baseline-Assessments) and at the cessation of the 6-month intervention (Post-Assessments). The potential moderating role of ApoE genotypes and the mediation role of BDNF will be explored. Participation in this study will take approximately 7 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Health Services Research

Official Title:

Effects of Multi-Domain Exercise Intervention on Memory Performance in Healthy Adults With and Without ApoE e4 Allele: A fMRI Study

Actual Study Start Date :

Apr 12, 2022

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multi-Domain Exercise Program Time: 6 months, total of 150 min of exercise per week. Intervention: aerobic training, muscular fitness training, balance, flexibility, meditation, and social interaction.	Behavioral: Multi-Domain Exercise Program The multi-domain exercise consisted of the main exercise (e.g., aerobic exercise, resistance exercise, flexibility training, and coordinative exercise), social interaction, and meditation. Participants are encouraged to engage in 150 min exercise per week consisting of one 90-min on-site session and multiple online sessions for 6 months.
Other: Control Group Time: 6 months, total of 60 min of online educational course per week. Intervention: educational materials relating to the effects of exercise on cognitive function and aging-related cognitive decline.	Behavioral: Control Group The "usual physical activity group," as the control group, is informed to maintain their lifestyles. In addition, participants are invited to attend one 60-min online educational course per week. The logs of physical activity behavior will be obtained from the participants once per month during the intervention period.

Arm

Intervention/Treatment

Experimental: Multi-Domain Exercise Program

Time: 6 months, total of 150 min of exercise per week. Intervention: aerobic training, muscular fitness training, balance, flexibility, meditation, and social interaction.

Behavioral: Multi-Domain Exercise Program

The multi-domain exercise consisted of the main exercise (e.g., aerobic exercise, resistance exercise, flexibility training, and coordinative exercise), social interaction, and meditation. Participants are encouraged to engage in 150 min exercise per week consisting of one 90-min on-site session and multiple online sessions for 6 months.

Other: Control Group

Time: 6 months, total of 60 min of online educational course per week. Intervention: educational materials relating to the effects of exercise on cognitive function and aging-related cognitive decline.

Behavioral: Control Group

The "usual physical activity group," as the control group, is informed to maintain their lifestyles. In addition, participants are invited to attend one 60-min online educational course per week. The logs of physical activity behavior will be obtained from the participants once per month during the intervention period.

Outcome Measures

Primary Outcome Measures

Changes in functional MRI indices [60 min each at the Baseline-Assessment and at the Post-Assessment]
Functional MRI assessments will be conducted at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment) to measure participants' brain functionalities. Changes in functional MRI indices between the Baseline-Assessment and Post-Assessment will be assessed.
Changes in working memory performance: N-back working memory task [30 min assessment time at the Baseline-Assessment and at the Post-Assessment]
Working memory performance will be assessed using the computerized n-back working memory task at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment). A total of 6 blocks with 108 trials (18 trials each block) will be utilized in the current study. Changes in working memory performance between the Baseline-Assessment and Post-Assessment will be assessed.
Changes in episodic memory performance: Relational and item-specific encoding and recognition test [30 min each session at the Baseline-Assessment and at the Post-Assessment]
Episodic memory performance will be assessed using the relational and item-specific encoding and recognition test at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment). Changes in episodic memory performance between the Baseline-Assessment and Post-Assessment will be assessed.

Secondary Outcome Measures

ApoE genotype [5 min at the Baseline Assessment]
Based on the genetic biomarkers (rs429358 and rs7412), participants' ApoE genotype will be determined.
Changes in blood neurotrophic marker: Brain-derived neurotrophic factor (BDNF) [5 min each at the Baseline-Assessment and at the Post-Assessment]
A 6 mL serum sample will be drawn from the antecubital vein at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment) to determine the concentration of BDNF. Changes in BDNF levels between the Baseline-Assessment and Post-Assessment will be assessed.
Physical fitness measurements: Changes in aerobic fitness [20 min each at the Baseline-Assessment and at the Post-Assessment]
Participants' aerobic fitness will be estimated using the submaximal cycle ergometer test at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment). Changes in aerobic fitness between the Baseline-Assessment and Post-Assessment will be assessed.
Physical fitness measurements: Changes in muscular fitness [15 min each at the Baseline-Assessment and at the Post-Assessment]
Muscular fitness will be assessed using either the push-up test/30sec or the chair stand test/30sec at the baseline (Baseline-Assessment) and the end of the 6-month intervention (Post-Assessment). A higher number completed indicated a better level of muscular fitness. Changes in muscular fitness between the Baseline-Assessment and Post-Assessment will be assessed.
Physical fitness measurements: Changes in flexibility [15 min each at the Baseline-Assessment and at the Post-Assessment]
Flexibility will be assessed using the sit-and-reach test at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment). Further distance indicates better lower back and hip joint flexibility. Changes in flexibility between the Baseline-Assessment and Post-Assessment will be assessed.
Physical fitness measurements: Changes in body composition [15 min each at the Baseline-Assessment and at the Post-Assessment]
The body composition (e.g., body water, body fat, skeletal muscle mass, body mass index, and percentage of body fat) will be assessed simultaneously using a body composition analyzer (ACCUNIQ BC380 Body Composition Analysis, SELVAS Healthcare Inc., Korea) at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment). Changes in body composition between the Baseline-Assessment and Post-Assessment will be assessed.
Psychosocial measures: Changes in mindfulness [5 min each at the Baseline-Assessment and at the Post-Assessment]
Levels of mindfulness will be assessed using the 15-items (1-6 Likert scale) WHOQOL-OLD-Taiwan Chinese version of the Mindful Attention Awareness Scale questionnaire at the baseline (Baseline-Assessment) and at the end of the 6-month intervention (Post-Assessment). Higher scores are associated with higher dispositional mindfulness. Changes in mindfulness levels between the Baseline-Assessment and Post-Assessment will be assessed.
Psychosocial measures: Changes in sleep quality [5 min each at the Baseline-Assessment and at the Post-Assessment]
Sleep quality is assessed by the Pittsburgh Sleep Quality Index. The questionnaire consists of 9 questions. Lower scores are associated with better sleep quality. Changes in sleep quality between the Baseline-Assessment and Post-Assessment will be assessed.
Psychosocial measures: Changes in depression [5 min each at the Baseline-Assessment and at the Post-Assessment]
Depression level is assessed by the Chinese version of the Geriatric Depression Scale (GDS-15). The questionnaire consists of 15 'Yes/No' items. The total scores between 5 and 9 indicate mild symptoms, and a score of 10 and above indicates moderate symptoms. Changes in depression levels between the Baseline-Assessment and Post-Assessment will be assessed.
Psychosocial measures: Changes in health-related quality of life [10 min each at the Baseline-Assessment and at the Post-Assessment]
Health-related quality of life is assessed by the 24-items (1-5 Likert scale) WHOQOL-OLD-Taiwan. The higher total scores indicate better quality of life. Changes in health-related quality of life between the Baseline-Assessment and Post-Assessment will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Normal or corrected-to-normal vision
Able to speak and read Chinese
Scores of Mini-Mental Status Examination >= 25
Physical Activity Readiness Questionnaire score < 0
Able to conduct the exercise with moderate intensity
Meet the criteria to undergo magnetic resonance imaging
Provide informed consent

Exclusion Criteria:

Diagnosed or self-reported cognitive problems (e.g., mild cognitive impairment or dementia)
Diagnosed or self-reported physical disease (e.g., untreated hypertension and chronic heart disease, stroke, brain tumor, musculoskeletal disorders, other exercise contradictions)
Diagnosed or self-reported major psychiatric illness (e.g., major depression, schizophrenia)
Diagnosed or self-reported neurodegenerative disease (e.g., Alzheimer's disease and other dementias, Parkinson's disease (PD) and PD-related disorders, Huntington's disease)
History of alcohol or drug abuse
History of chemotherapy
Traveling consecutively for three weeks or more during the study
Unwillingness to be randomized to one of the two groups
Currently participating in another study trial

Exclusion Criteria for functional magnetic resonance images (fMRI):

Participants will be excluded if s/he has a contraindication to fMRI scanning, such as aneurysm clip, implanted neural stimulator, cochlear implant, any implanted device, cardiac pacemaker. To ensure volunteers are eligible for the current project, they will be asked to fill out a questionnaire to inform whether they have conditions (e.g. paralyzed hemidiaphragm) or present unnecessary risks (e.g., pregnancy) during the recruitment period.